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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 451 records · Page 25Linked to original sources
PubMed1989

Neuropsychological consequences of volatile substance abuse: a population based study of secondary school pupils.

OBJECTIVE: To examine the effects of volatile substance abuse on neuropsychological functioning. DESIGN: A sample of index children and matched controls were identified by a two stage procedure. Firstly, over 5000 secondary school pupils completed a screening questionnaire, and, secondly, a sample of those who acknowledged volatile substance abuse and a matched sample of those who denied the practice were assessed in detail by means of (a) individually conducted interviews and (b) toxicological examination of breath samples (to exclude those intoxicated at the time of testing). SETTING: 16 Local education authority secondary schools in London. SUBJECTS: 160 Pupils aged 13-16: 80 index children who had abused volatile substances to the point of intoxication at least once (confirmed by interview) and 80 controls (confirmed by interview) matched for school year, sex, and ethnic background. MEASUREMENTS AND MAIN RESULTS: Neuropsychological functioning tests provided 35 main outcome measures and were administered blind. Data on educational test performance before substance abuse began were obtained retrospectively. Information on potentially confounding social factors, such as number of siblings, tenure of housing, and parents' socioeconomic and employment state was also obtained. The index children performed significantly less well than the controls in tests of vocabulary, verbal intelligence quotient, full scale intelligence quotient, and a measure of impulsivity. When background social disadvantage was taken into account these differences were no longer significant. There were no significant associations between performance on psychological testing and frequency of abuse, and relations with other aspects of the children's history of abuse were generally weak or unsystematic. Comparisons between the results of these tests and of educational tests taken before substance abuse produced equivocal findings. CONCLUSION: Volatile substance abuse, as commonly practised by secondary school pupils, is unlikely to result in neuropsychological impairment.

Adolescent↗
PubMed1989

Prevalence and diagnosis of chronic respiratory symptoms in adults.

OBJECTIVE: To investigate the prevalence and diagnosis of chronic respiratory disease in adults. DESIGN: Screening questionnaire was sent to all patients aged 40-70 on the register of a group general practice; those responding positively were sent a detailed questionnaire and invited for assessment of respiratory function by forced expiratory volume in one second, forced vital capacity, peak flow rate, and reversibility studies with a beta adrenergic inhaler. SETTING: Group general practice in south west London. RESULTS: Of 2387 patients aged 40-70, 1444 completed a screening questionnaire. Of the 509 patients who reported cough, phlegm, wheeze, or shortness of breath, 324 responded to a detailed questionnaire, 256 of whom had simple respiratory function assessed. Chronic bronchitis affected 106 (17%) men and 58 (7%) women, and wheeze occurring at least once a week affected 60 (9%) men and 20 (3%) women. Only a half to a third of patients had received a diagnostic label of chronic bronchitis or asthma for their symptoms. There was considerable clinical and physiological similarity (including reversibility of the airways) between patients labelled as having asthma and having chronic bronchitis. A label of asthma was used more often for patients of social classes I and II. CONCLUSIONS: Comparison with prevalence surveys carried out in the 1950s showed that respiratory symptoms are as common now as then, but the risk of disabling chronic bronchitis has fallen, more among men than women, probably because of their reduced smoking. Changes in diagnostic fashion, together with increased detection, may have contributed to the upward trend in reported morbidity from asthma over the past 30 years.

Adult↗
PubMed1989

Mononuclear leucocyte function in patients with lichen planus and cutaneous lupus erythematosus during chemotherapy with clofazimine.

Mitogen-induced transformation and the production of reactive oxidants by mononuclear leucocytes (MNLs) from patients with chronic dermatological disorders were investigated in vitro before and during the administration of the antimycobacterial/immunosuppressive agent clofazimine (200 mg 3 times weekly). Seven patients, 4 with lichen planus and 3 with cutaneous lupus erythematosus, were included in the study. Clofazimine administration did not influence the mitogen-induced proliferative responses of patients' MNLs. However, chemotherapy with this drug stimulated the production of reactive oxidants by MNLs. Since reactive oxidants are immunosuppressive it is possible that these effects may be involved in the pharmacotherapeutic activity of clofazimine.

Adolescent↗
PubMed1989

Investigation of the relationships between plasma levels of ascorbate, vitamin E and beta-carotene and the frequency of sister-chromatid exchanges and release of reactive oxidants by blood leucocytes from cigarette smokers.

In this study the frequencies of sister-chromatid exchanges (SCEs) were correlated with measurements of the release of reactive oxidants by phagocytes, as determined by luminol-enhanced chemiluminescence (LECL), and levels of the anti-oxidants ascorbate, beta-carotene and vitamin E in blood specimens taken from 65 young asymptomatic cigarette smokers. Increased SCE frequencies correlated with LECL responses (p less than 0.0075) of activated blood phagocytes. Anti-oxidant levels did not correlate with either LECL or SCEs. These findings indicate that increased generation of reactive oxidants by circulating phagocytes from cigarette smokers are associated with cytogenetic changes.

Adult↗
PubMed1989

Increased frequency of oxidant-mediated DNA strand breaks in mononuclear leucocytes exposed to activated neutrophils from cigarette smokers.

Following activation with the synthetic chemotactic tripeptide FMLP, potentiated by cytochalasin B (CB), blood neutrophils from cigarette smokers generated greater amounts of both extracellular and intracellular reactive oxidants than cells from non-smoking control subjects. FMLP/CB-activated neutrophils from cigarette smokers also inflicted increased oxidant-mediated damage to the DNA of cocultured mononuclear leucocytes, which was prevented by the inclusion of superoxide dismutase and catalase individually and in combination. These observations demonstrate that cigarette smoking primes phagocytes to generate increased amounts of potentially carcinogenic reactive oxidants.

Catalase↗
PubMed1989

Erythromycin and roxithromycin potentiate human neutrophil locomotion in vitro by inhibition of leukoattractant-activated superoxide generation and autooxidation.

Erythromycin and especially roxithromycin (1.25-20 micrograms/mL) stimulated neutrophil migration in vitro. Both antibiotics selectively inhibited superoxide generation by neutrophils activated with the N-formylated leukotactic tripeptide FMLP, the calcium ionophore A23187 and the pharmacologic agent benoxaprofen, while the responses initiated by the tumor promotor PMA and opsonized zymosan were unaffected. Neutrophil autooxidation during exposure to FMLP was also decreased by both antibiotics. The antimicrobial agents did not scavenge superoxide. Likewise, the interactions of [3H]FMLP with specific receptors on neutrophils, FMLP-activated degranulation and intracellular calcium fluxes, the activity of cytosolic protein kinase C and the release of [3H]arachidonate from calcium ionophore-stimulated neutrophils were all unaffected by the antibiotics. Erythromycin and roxithromycin in particular appear to enhance neutrophil migration by an antioxidant mechanism that is not due to inhibition of transductional events involved in the activation of NADPH-oxidase or to oxidant scavenging properties.

Calcimycin↗
PubMed1989

Investigation of the structural properties of dihydrophenazines which contribute to their pro-oxidative interactions with human phagocytes.

Twenty-six dihydrophenazine compounds, including clofazimine, were investigated, at a fixed concentration of 1 mg/l, for their effects on spontaneous and stimulus-activated generation of superoxide by human neutrophils in vitro. The synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L phenyl-alanine (FMLP) (0.1 microM) was used as a stimulant of membrane-associated oxidative metabolism. None of the agents tested influenced basal levels of superoxide generation by neutrophils. However sixteen of these compounds, all rimino phenazines, significantly increased the production of superoxide by FMLP-activated neutrophils. These pro-oxidative, priming interactions of the rimino phenazines with neutrophils were largely dependent on the nature of the alkylimino group at position 2 on the phenazine nucleus, and to a lesser extent on halogenation. Cycloalkylimino groups were generally less potent stimulants of superoxide generation by FMLP-activated neutrophils than clofazimine, and their pro-oxidative properties were independent of mono- or dichlorination. However the halogen-free cycloalkylimino compound, B669, was an exceptionally potent pro-oxidative agent. Chlorination was promotive to pro-oxidative activity in the case of dihydrophenazines with linear or branched alkylimino substituents. The pharmaco-therapeutic mechanisms of dihydrophenazines may be related to their pro-oxidative interactions with phagocytes.

Clofazimine↗
PubMed1989

Mutation of host cell determinants which discriminate between lytic and persistent mouse hepatitis virus infection results in a fusion-resistant phenotype.

The expression of mouse hepatitis virus (MHV) E2-specific mRNA, the E2 polypeptide and its associated cell fusing activity was monitored in various cell types inoculated with a recombinant vaccinia virus, designated vMS containing the E2 gene. The results suggest that host cell permissiveness to MHV infection correlates with cellular susceptibility to membrane fusion mediated by the MHV E2 glycoprotein. In addition, we utilized a genetic approach to the analysis of host cell functions involved in determining permissiveness to MHV. By using the chemical mutagen ethyl methanesulphonate, mouse fibroblast cell mutants were generated and selected for their resistance to cell killing by MHV. When challenged with MHV, all five mutants examined gave rise to persistent infections, in contrast to wild-type L-2 cells which were rapidly killed by the virus. The results provide genetic evidence in support of a previous correlation proposed between MHV permissiveness and two host determinants, namely susceptibility to MHV infection and to MHV-mediated cell fusion. Fusion resistance was specific to fusion mediated by the MHV E2 glycoprotein as shown in contact fusion assays between uninfected cells and cells infected either with MHV or with an E2-expressing recombinant vaccinia virus. In contrast, mutant cells were not resistant to fusion after treatment with polyethylene glycol. The observed high rate of generation of these mutants suggests that the conversion of a fully MHV-susceptible cell to a semi-resistant one is a fairly common event, possibly involving a single mutation. In this case, resistance to MHV infection and to E2-mediated membrane fusion may depend on a common host function. This result provides prospects for the precise genetic and biochemical characterization of the steps involved in host cell permissiveness to MHV infection.

Animals↗
PubMed1989

A model for persistent murine coronavirus infection involving maintenance via cytopathically infected cell centres.

The relatively cell impermeable hygromycin B was found to inhibit viral but not cellular protein synthesis when added to cultures of murine hepatitis virus (MHV)-infected or mock-infected mouse L-2 fibroblasts. Membrane permeability, as judged by influx of sodium ions, has previously been demonstrated to be an MHV E2 glycoprotein-mediated, cytopathic effect of MHV infection in L-2 cells. It is therefore likely that the selective effect of hygromycin B on viral protein synthesis is a reflection of an increased drug penetration into virus-infected cells. Using hygromycin B as a marker for MHV-induced cell membrane cytopathology, the effects of drug treatment on a persistent MHV infection in mouse LM-K fibroblasts were investigated. MHV persistence in LM-K cells, which normally involves a steady state infection of 0.1 to 1% of the cells in culture, was found to be cured by hygromycin B treatment, as measured by the elimination of infectious virus from the supernatant medium. Hygromycin B also resulted in the eradication of MHV-specific RNA from LM-K cells, arguing against the presence of a non-cytopathically or latently infected subpopulation of cells.

Animals↗
PubMed1989

Dithranol-mediated, dose-dependent priming and activation of luminol-enhanced chemiluminescence responses of human neutrophils in vitro.

At concentrations of 10 micrograms/ml and greater, dithranol (anthralin) caused an intense, dose-related activation of luminol-enhanced chemiluminescence (LECL) of human neutrophils and also increased oxygen consumption by these cells. Activation of LECL, which was maximal with 40 micrograms/ml dithranol, occurred promptly, peaked at 3-5 min, then declined. Dithranol-mediated stimulation of LECL was inhibited by catalase and by the protein kinase C inhibitor, H-7. Neutrophils from individuals with chronic granulomatous disease were unresponsive to the pro-oxidative effects of dithranol. At concentrations of 2.5 micrograms/ml and less, dithranol did not directly activate the LECL responses of neutrophils. However pre-treatment of neutrophils with dithranol at concentrations of 0.5-2.5 micrograms/ml increased the LECL-responses of cells subsequently stimulated with calcium ionophore and opsonized zymosan. These observations demonstrate two distinct dose-related, pro-oxidative interactions of dithranol with human neutrophils: low-dose priming and high-dose activation of oxidant generation. Since phagocyte-derived reactive oxidants are immunosuppressive, these pro-oxidative interactions of dithranol with human neutrophils may contribute to the pharmacotherapeutic mechanisms of this agent.

Adult↗
PubMed1989

Treatment of adult asthma: is the diagnosis relevant?

The diagnosis and management of chronic respiratory symptoms was studied in all adults aged 40-70 years in a group general practice. A respiratory symptoms screening questionnaire was sent to 2387 men and women, of whom 1444 (85% of those who had not moved or died) responded. The 509 subjects reporting symptoms were sent a detailed questionnaire and invited to have their respiratory function tested. Of these, 324 (64%) responded, of whom 256 (79%) had spirometry. A diagnosis of chronic bronchitis was reported by 3.9% of the men and 2.1% of the women, and a diagnosis of asthma by 4.7% of the men and 3.3% of the women. Wheezing in the preceding year was reported by 18% of the men and 15% of the women, and 16.7% of the men and 7.1% of the women satisfied the Medical Research Council criteria for chronic bronchitis. Bronchodilator treatment was being taken by 12% of the patients with symptoms, regular cough linctus by 10%, and regular antibiotics by 5%. After the frequency and severity of respiratory symptoms had been controlled for wheezing patients reporting a diagnosis of asthma were prescribed bronchodilatory drugs three times more often than those labelled as having chronic bronchitis and 12 times more often than those without a diagnostic label. Eleven per cent of general practitioner consultations resulted in a referral to hospital. Referral was unrelated to the diagnosis given, but depended on the degree of respiratory disability and handicap experienced by the patient. Our findings confirm the relevance of the diagnostic label to the drug management of chronic wheezing disorders, but further investigation of the diagnostic process is needed to establish why some patients with severe wheeze remain untreated.

Adult↗
PubMed1989

An in vitro investigation of the intraphagocytic bioactivity of difloxacin, ciprofloxacin, pefloxacin and fleroxacin.

In this study the intraphagocytic bioactivity of difloxacin, ciprofloxacin, pefloxacin and fleroxacin was investigated using human neutrophils and a combination of a radioassay, a colony-counting method and a fluorescence microassay which enables us to differentiate between intracellular bacteriostatic and bactericidal mechanisms. Staphylococcus aureus and Listeria monocytogenes were used as the test intraphagocytic microbial pathogens. It was found that difloxacin, ciprofloxacin and to a lesser extent pefloxacin and fleroxacin possess intracellular bacteriostatic activity for S. aureus and L. monocytogenes.

Adult↗
PubMed1989

Spirometric abnormalities in young smokers correlate with increased chemiluminescence responses of activated blood phagocytes.

Spirometric values determined from the flow-volume loops of 60 healthy young smokers (mean age, 28 +/- 0.6 yr) were correlated with measurements of the release of extracellular and intracellular reactive oxidants (RO) as determined by luminol-enhanced chemiluminescence (LECL) from peripheral blood activated with the synthetic chemotactic tripeptide FMLP combined with cytochalasin B (CB). Fractionation and reconstitution experiments revealed that LECL originated predominantly from polymorphonuclear leukocytes (PMNL). Circulating total leukocyte counts and serum thiocyanate levels were also determined. The data were analyzed using Spearman's correlation coefficient and by multiple regression analysis. Cigarette smoking was associated with elevated intracellular and especially extracellular LECL responses, the latter being strongly correlated (p less than 0.0001) with cigarettes smoked per day, serum thiocyanate levels, circulating leukocytes, and PMNL counts. Abnormalities of the spirometric parameters FEV1/FVC, FEF50/FVC, FEF25, FEF25-75, and FEF75-85 correlated best with extracellular LECL (p less than 0.0002 to p less than 0.0001), but also with pack-years (p less than 0.006 to p less than 0.0001), cigarettes smoked per day (p less than 0.008 to p less than 0.0002), thiocyanate levels (p less than 0.04 to p less than 0.002) and leukocyte counts (p less than 0.03 to p less than 0.002). According to stepwise multiple regression analysis of the data the combination of the independent variables extracellular LECL, pack-years, and numbers of circulating PMNL accounts for 35.6% of the variation in lung function in the group of cigarette smokers, with LECL being the most important contributor (26%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Fetal femur length to detect trisomy 21. A reappraisal.

An association between short femur length (FL) relative to the biparietal diameter (BPD) measured in the second trimester and the Down syndrome recently has been reported by Benacerraf et al (1987). Fetuses meeting an easily calculated criterion were stated to have a high probability for trisomy 21. We compared the biometric data from a selected group of 229 normal second trimester fetuses with 30 fetuses of similar gestational age with karyotype-proven trisomy 21. We found a substantial difference in femur lengths of normal fetuses in our population compared to that reported by Benacerraf et al. The reason for the difference is unclear. Further, we were unable to demonstrate a statistically discernible deviation of measured versus predicted femur lengths in the Down syndrome cohort employing either the formula recommended by Benacerraf et al or a formula calculated from our normal cohort.

Biometry↗
PubMed1989

Characterization of a novel myeloma cell line, MM.1.

A myeloma cell line, MM.1, has been established from the peripheral blood cells of a patient with immunoglobulin A myeloma. MM.1 grows in suspension either singly or in small clusters and secretes lambda-light chain. Phenotypically, MM.1 cells lack most B cell antigens, but they do express human leukocyte antigen DR, PCA-1, and T9 and T10 antigens. Molecular analysis of MM.1 demonstrates that it is negative for the presence of the Epstein-Barr virus genome. Southern analysis of MM.1 detected a rearrangement of the lambda-light chain gene, and Northern analysis revealed high levels of lambda gene expression. Cytogenetic analysis of the MM.1 cell line revealed the presence of seven related chromosomally abnormal cell lines characterized by numerical and structural aberrations, and it revealed five nonclonal abnormal cells. The most notable abnormality is a reciprocal translocation involving band q24.3 of chromosome 12 and band q32.3 of chromosome 14; translocations involving 14q32 are frequently observed in neoplasms of B cell origin.

Adult↗